Aire expression in the thymus contributes to immune tolerance by eliminating auto-reactive T cells; insufficient elimination causes autoimmune disorders. The Aire gene was thought to be expressed only in the thymus, but recently, researchers reported Aire expression in peripheral lymph nodes. Researchers have now identified the cells expressing Aire in 0.01% of lymph node cells to be ILC3-like cells using Aire-reporter mice and flow cytometry. The results may lead to elucidation of the causes of autoimmune disorders and treatments.
Peripheral lymph nodes
The thymus is the organ in which T cells differentiate. T cells express receptors that react with pathogenic microbes and viruses. However, the thymus generates auto-reactive T cells that react with self antigens, which must therefore be eliminated in the thymus. The mechanism for elimination of auto-reactive T cells is referred to as central tolerance.
Medullary thymic epithelial cells play key roles in central tolerance. These cells express organ-specific antigens (tissue-restricted antigens). For example, insulin is produce only by pancreatic β cells and C-reactive protein is produce only in the liver. The medullary thymic epithelial cells produce and present such proteins to T cells and eliminate those T cells that react with them, i.e. auto-reactive T cells.
Pathogenesis in multiple organs
Aire is a gene that regulates expression of tissue-restricted antigens in medullary thymic epithelial cells. Mutation of Aire causes decreased expression levels of tissue-restricted antigens in the thymus, and consequently, elimination of auto-reactive T cells becomes insufficient. This is thought to lead to autoimmune disease pathogenesis in multiple organs such as ACEPED.
It was believed that Aire is express only in the thymus; but several research groups recently present evidence that some cells in peripheral lymph nodes express Aire; peripheral lymph nodes are the organs in which immune reactions take place. However; there is disagreement between research groups on Aire-expressing cell types.
Thus, cells expressing the Aire gene in lymph nodes were analyze in detail using two strains of Aire-reporter mice and high sensitivity flow cytometry using Aire antibody. This confirmed that a very small number of cells; 0.01% of the population of all the cells in lymph nodes, did indeed express Aire.